BIOACTIVE MARINE MICROBIAL METABOLITES

生物活性海洋微生物代谢物

• 批准号: 2882202
• 负责人: Hao Chen
• 金额: $ 38.16万
• 依托单位: NOVASCREEN BIOSCIENCES CORPORATION
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-09-01 至 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2882202
• 关键词: Candida; Enterococcus; Escherichia coli; Pseudomonas aeruginosa; Staphylococcus aureus; anaerobic bacteria; antibacterial agents; antiinflammatory agents; aquatic organism; biological products; chemical structure; drug discovery /isolation; drug resistance; drug screening /evaluation; guinea pigs; high performance liquid chromatography; laboratory mouse; mass spectrometry; microorganism; microorganism culture; nuclear magnetic resonance spectroscopy; pharmacology; receptor binding

This SBIR Phase II Grant Application has as its goal the discovery, development and commercialization of new, small molecule drugs which have their origin as natural products elaborated by marine microorganisms. Initial disease targets for drug development include: i) new antibiotics which are broadly effective against microbial pathogens and are effective in controlling pathogens resistant to currently utilized antibiotic drugs, and ii) new drugs able to modulate inflammatory process and suppress subsequent allergic responses. Marine microorganisms represent a vast, unexplored, and promising source material for the discovery of novel drugs. Work completed under Phase I of this Application was successful in establishing routine methods and manipulations to circumvent difficulties traditionally associated with drug discovery efforts employing marine microorganisms. These inherent difficulties include the isolation and growth of marine microorganisms, the stimulation of bioactive material production, and the removal or suppression of interfering media components during bioassay. Phase I work also resulted in the discovery of more than 20 highly active materials. Work proposed under Phase II represents the application and expansion of these routine methods and manipulations to a substantial bioactive materials discovery and development effort. The screening program will employ: i) a collection of taxonomically heterogeneous marine microbial isolates collected from widely diverse geographic regions and ecological niches, and ii) a battery of antibiotic assays, and targeted receptor binding based pharmacological assays. The active materials discovered in the screening component are advanced through assay guided fractination for compound isolation and prufication followed by a chemistry intensive effort focused on determining the structure of the active chemical moity. The most active drug materials will be advanced to pre-clinical development. PROPOSED COMMERCIAL APPLICATION Successful development and application of the proposed technology should revitalize the flow of novel, small molecule, natural product drug candidates into preclinical safety and efficacy testing programs. This Phase II Grant program is specially focused on developing new drugs to treat important disease categories comprising; I infectious diseases including those infections resulting from antibiotic resistant pathogens and ii) new treatment for inflammation and allergy.

该 SBIR 第二阶段拨款申请的目标是发现， 新的小分子药物的开发和商业化 其起源是海洋精制的天然产品 微生物。 药物开发的初始疾病目标包括： i) 对微生物广泛有效的新型抗生素 病原菌，并能有效控制具有抗药性的病原菌 目前使用的抗生素药物，以及 ii) 能够调节的新药物 炎症过程并抑制随后的过敏反应。 海洋 微生物是一个巨大的、未开发的、有前途的来源 发现新药的材料。 阶段已完成的工作 我的这个应用程序成功地建立了常规方法和 为规避传统上与相关问题相关的困难而进行的操纵 利用海洋微生物的药物发现工作。 这些固有的 困难包括海洋微生物的分离和生长， 刺激生物活性物质的产生，以及去除或 在生物测定过程中抑制干扰介质成分。 第一阶段 工作还发现了 20 多个高度活跃的 材料。 第二阶段提出的工作代表了应用程序和 将这些常规方法和操作扩展到实质性 生物活性材料的发现和开发工作。 筛选 计划将采用：i）分类学上异质的集合 从广泛不同的地理区域收集的海洋微生物分离株 区域和生态位，以及 ii) 一系列抗生素检测， 和基于靶向受体结合的药理学测定。 活跃的 筛选组件中发现的材料通过 用于化合物分离和纯化的测定引导分馏 接下来是化学密集的努力，重点是确定 活性化学基团的结构。 最活跃的药物材料 将进入临床前开发阶段。 拟议的商业应用 所提出的技术的成功开发和应用应该 重振新型小分子天然产物药物的流动 候选者参与临床前安全性和有效性测试计划。 这 第二阶段资助计划特别侧重于开发新药 治疗重要的疾病类别，包括；我传染病 包括由抗生素耐药病原体引起的感染 ii) 针对炎症和过敏的新疗法。